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Sci. STKE, 10 June 2003
Vol. 2003, Issue 186, p. tw220
[DOI: 10.1126/stke.2003.186.tw220]


PHOSPHATASES Cholesterol Controls ERK Activity

Cholesterol is a major component of membrane microdomains, such as caveolae, which are also enriched in the protein caveolin, and lipid rafts. Depletion of cholesterol can alter the signaling properties of cells. Wang et al. show that treatment of cultured cells with the cholesterol adsorbing resin methyl-β-cyclodextrin (CD) increased the amount of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) in both the cytosol and in caveolae. CD decreased the activity of cytosolic serine and threonine and tyrosine phosphatase activities in an assay using phosphorylated ERK2-glutathione-S-transferase fusion protein (pERK2-GST) as the substrate. Column chromatography was used to identify a ~440-kD complex enriched in the ERK1/2 phosphatase activity that also contained protein phosphatase (PP) 2AC and PP2AB as seen by immunoblotting. The phosphatase activity of these fractions was decreased in cells treated with CD. Using cells transfected with an epitope-tagged version of the tyrosine phosphatase HePTP, this phosphatase was also determined to be part of the ERK1/2 phosphatase complex. Coprecipitation assays determined that the association between HePTP and PP2A was disrupted by treatment of the cells with CD to decrease cholesterol. Thus, the increased ERK signaling associated with cholesterol depletion may be explained by the loss of an ERK phosphatase complex.

P.-y. Wang, P. Liiu, J. Weng, E. Sontag, R. G. W. Anderson, A cholesterol-regulated PP2A/HePTP complex with dual specificity ERK1/2 phosphatase activity. EMBO J. 22, 2658-2667 (2003). [Abstract] [Full Text]

Citation: Cholesterol Controls ERK Activity. Sci. STKE 2003, tw220 (2003).

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